DESCRIPTION(provided by applicant): We propose renewal of the Specialized Program of Research Excellence (SPORE) in Breast Cancer at the UNC Lineberger Comprehensive Cancer Center for Years 10-14. One of four Breast Cancer SPOREs funded in 1992, the UNC SPORE?s unique goals emphasize multidisciplinary translational research that spans and links the population, clinical, and basic sciences, as well as emphasizing health disparities between African-American and Caucasian populations. The UNC Breast Cancer SPORE?s primary objectives are to: Population Science: Maintain and analyze two long-term, large, population-based studies (Carolina Breast Cancer Study; Long Island Breast Cancer Study) of invasive breast cancer and carcinoma in situ that have epidemiologic/risk data, tumor samples, blood, and germline DNA; use these studies to test hypotheses regarding breast cancer etiology, prognosis, progression, and response to therapy, as well as investigate disparities in incidence, mortality, and morbidity between African-American and Caucasian women. Clinical/Translational Science: Maintain an infrastructure for performing innovative, institutional breast cancer clinical trials providing human tissue endpoints for translational research projects; In specific projects: a) determine how to break self-tolerance to expressed antigens on breast cancer cells and use this information to clinical immunotherapeutic advantage; b) study breast cancer patients? genotype and somatic mutations and relate these to prognosis and response to therapy; c) analyze by cDNA micro array breast cancer gene expression before and after therapy to devise new markers of prognosis and response to therapy; and d) devise novel approaches to enhancing breast cancer chemotherapy efficacy based on knowledge of intracellular cell survival signaling and its inhibition; Core Facilities: Establish, maintain, and improve core facility technology to: (1) study somatic mutations in small human tumor samples; (2) perfect high-throughput genotyping of germline DNA; (3) analyze mRNA expression in cells and tumors using cDNA microarray; (4) validate new antibodies and FISH probes to analyze specific gene products in fresh and archival tumor samples; and (5) establish and maintain a data management, informatics, and analysis infrastructure. Development and Inter-SPORE Collaboration: Promote translational research projects through developmental pilot projects and recruit new investigators to breast cancer research; and Use our emphasis on population-based molecular epidemiology, minority health disparities, genomics and clinical research to enter into productive collaboration with other Breast Cancer SPOREs.